CAMAU_SCOPA
ID CAMAU_SCOPA Reviewed; 33 AA.
AC P60254;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 1.
DT 25-MAY-2022, entry version 74.
DE RecName: Full=Maurocalcin {ECO:0000303|PubMed:27114612};
DE Short=MCa {ECO:0000303|PubMed:10713267, ECO:0000303|PubMed:10861934};
DE AltName: Full=Maurocalcine {ECO:0000303|PubMed:10713267, ECO:0000303|PubMed:10861934};
OS Scorpio palmatus (Israeli golden scorpion) (Scorpio maurus palmatus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Scorpioninae; Scorpio.
OX NCBI_TaxID=1662106;
RN [1]
RP PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, TOXIC DOSE, AND MASS SPECTROMETRY.
RX PubMed=10713267; DOI=10.1016/s0014-5793(00)01239-4;
RA Fajloun Z., Kharrat R., Chen L., Lecomte C., Di Luccio E., Bichet D.,
RA El Ayeb M., Rochat H., Allen P.D., Pessah I.N., De Waard M.,
RA Sabatier J.-M.;
RT "Chemical synthesis and characterization of maurocalcine, a scorpion toxin
RT that activates Ca(2+) release channel/ryanodine receptors.";
RL FEBS Lett. 469:179-185(2000).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF LYS-8; LYS-19; LYS-20; LYS-22; ARG-23; ARG-24
RP AND THR-26.
RX PubMed=12869557; DOI=10.1074/jbc.m305798200;
RA Esteve E., Smida-Rezgui S., Sarkozi S., Szegedi C., Regaya I., Chen L.,
RA Altafaj X., Rochat H., Allen P., Pessah I.N., Marty I., Sabatier J.M.,
RA Jona I., De Waard M., Ronjat M.;
RT "Critical amino acid residues determine the binding affinity and the Ca2+
RT release efficacy of maurocalcine in skeletal muscle cells.";
RL J. Biol. Chem. 278:37822-37831(2003).
RN [3]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=17291197; DOI=10.1042/bj20061404;
RA Shahbazzadeh D., Srairi-Abid N., Feng W., Ram N., Borchani L., Ronjat M.,
RA Akbari A., Pessah I.N., De Waard M., El Ayeb M.;
RT "Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus
RT which is active on ryanodine-sensitive Ca2+ channels.";
RL Biochem. J. 404:89-96(2007).
RN [4]
RP MUTAGENESIS OF ASP-2; LEU-4; PRO-5; HIS-6; LEU-7; LYS-8; LEU-9; GLU-12;
RP ASN-13; ASP-15; LYS-19; LYS-20; ARG-23; ARG-24 AND THR-26.
RX PubMed=17888395; DOI=10.1016/j.bbamem.2007.06.030;
RA Mabrouk K., Ram N., Boisseau S., Strappazzon F., Rehaim A., Sadoul R.,
RA Darbon H., Ronjat M., De Waard M.;
RT "Critical amino acid residues of maurocalcine involved in pharmacology,
RT lipid interaction and cell penetration.";
RL Biochim. Biophys. Acta 1768:2528-2540(2007).
RN [5]
RP FUNCTION OF THE SYNTHETIC D-MAUROCALCINE.
RX PubMed=20610396; DOI=10.1074/jbc.m110.104919;
RA Poillot C., Dridi K., Bichraoui H., Pecher J., Alphonse S., Douzi B.,
RA Ronjat M., Darbon H., De Waard M.;
RT "D-Maurocalcine, a pharmacologically inert efficient cell-penetrating
RT peptide analogue.";
RL J. Biol. Chem. 285:34168-34180(2010).
RN [6]
RP FUNCTION, SYNTHESIS, AND 3D-STRUCTURE MODELING.
RX PubMed=27114612; DOI=10.1085/jgp.201511499;
RA Xiao L., Gurrola G.B., Zhang J., Valdivia C.R., SanMartin M., Zamudio F.Z.,
RA Zhang L., Possani L.D., Valdivia H.H.;
RT "Structure-function relationships of peptides forming the calcin family of
RT ryanodine receptor ligands.";
RL J. Gen. Physiol. 147:375-394(2016).
RN [7]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=10861934;
RX DOI=10.1002/1097-0134(20000815)40:3<436::aid-prot90>3.0.co;2-9;
RA Mosbah A., Kharrat R., Fajloun Z., Renisio J.-G., Blanc E., Sabatier J.-M.,
RA El Ayeb M., Darbon H.;
RT "A new fold in the scorpion toxin family, associated with an activity on a
RT ryanodine-sensitive calcium channel.";
RL Proteins 40:436-442(2000).
CC -!- FUNCTION: This toxin stabilizes ryanodine receptor 1 (RyR1) opening in
CC a long-lasting subconductance state (48%-60% of the full conductance
CC state) (PubMed:10713267, PubMed:12869557, PubMed:27114612).
CC Furthermore, it triggers calcium release from sarcoplasmic vesicles
CC (6.6 nM are enough to induce a sharp release, and 60% of the total
CC calcium is released after toxin (100 nM) addition) probably by acting
CC as a cell-penetrating peptide (CPP) (PubMed:27114612). In addition, it
CC has been shown to dose-dependently stimulate ryanodine binding to RyR1
CC (EC(50)=12.5-26.4 nM) (PubMed:12869557, PubMed:17291197,
CC PubMed:17888395, PubMed:27114612). It also augments the bell-shaped
CC calcium-[3H]ryanodine binding curve that is maximal at about 10 uM
CC calcium concentration (PubMed:27114612). It binds a different site as
CC ryanodine (PubMed:10713267). It acts synergistically with caffeine (By
CC similarity). In vivo, intracerebroventricular injection into mice
CC causes death (PubMed:10713267). {ECO:0000250|UniProtKB:A0A1L4BJ42,
CC ECO:0000250|UniProtKB:B8QG00, ECO:0000250|UniProtKB:P59868,
CC ECO:0000269|PubMed:10713267, ECO:0000269|PubMed:12869557,
CC ECO:0000269|PubMed:17291197, ECO:0000269|PubMed:17888395,
CC ECO:0000269|PubMed:27114612}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:10713267}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10713267}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:10861934}.
CC -!- PTM: The non-natural D-maurocalcin (a chiral analog of maurocalcin
CC composed of D-amino acids) completely loses the ability to stimulate
CC [3H]ryanodine binding and calcium release. Its protease resistance,
CC combined with its efficient cell penetration at concentrations devoid
CC of cell toxicity, suggests that it should be an excellent vector for in
CC vivo applications. {ECO:0000269|PubMed:20610396}.
CC -!- MASS SPECTROMETRY: Mass=3858.2; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:10713267};
CC -!- TOXIC DOSE: LD(50) is 1 mg/kg mice by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:10713267}.
CC -!- SIMILARITY: Belongs to the scorpion calcin family. {ECO:0000305}.
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DR PDB; 1C6W; NMR; -; A=1-33.
DR PDBsum; 1C6W; -.
DR AlphaFoldDB; P60254; -.
DR BMRB; P60254; -.
DR SMR; P60254; -.
DR TCDB; 8.B.16.1.1; the maurocalcine (maca) family.
DR EvolutionaryTrace; P60254; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019855; F:calcium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR012632; Scorpion_calcine.
DR Pfam; PF08099; Toxin_27; 1.
DR PROSITE; PS60028; SCORPION_CALCINE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW Ryanodine-sensitive calcium-release channel impairing toxin; Secreted;
KW Toxin.
FT PEPTIDE 1..33
FT /note="Maurocalcin"
FT /evidence="ECO:0000269|PubMed:10713267"
FT /id="PRO_0000044950"
FT REGION 22..24
FT /note="Essential for stimulation of [3H]ryanodine binding
FT to RYR"
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT SITE 8
FT /note="Important for stimulation of [3H]ryanodine binding
FT to RYR"
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT SITE 19
FT /note="Mildly important for stimulation of [3H]ryanodine
FT binding to RYR"
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT SITE 20
FT /note="Mildly important for stimulation of [3H]ryanodine
FT binding to RYR"
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT SITE 26
FT /note="Mildly important for stimulation of [3H]ryanodine
FT binding to RYR"
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT SITE 31
FT /note="Essential for stimulation of [3H]ryanodine binding
FT to RYR1"
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT SITE 33
FT /note="Essential for stimulation of [3H]ryanodine binding
FT to RYR1"
FT /evidence="ECO:0000250|UniProtKB:P59868"
FT DISULFID 3..17
FT /evidence="ECO:0000269|PubMed:10861934,
FT ECO:0000312|PDB:1C6W"
FT DISULFID 10..21
FT /evidence="ECO:0000269|PubMed:10861934,
FT ECO:0000312|PDB:1C6W"
FT DISULFID 16..32
FT /evidence="ECO:0000269|PubMed:10861934,
FT ECO:0000312|PDB:1C6W"
FT MUTAGEN 2
FT /note="D->A: Biotinylated maurocalcin: 3-fold increase of
FT stimulation of [3H]ryanodine binding to RYR1, and no change
FT in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 4
FT /note="L->A: Biotinylated MCa: No significant change in
FT stimulation of [3H]ryanodine binding to RYR1, and low
FT decrease in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 5
FT /note="P->A: Biotinylated MCa: 4-fold increase of
FT stimulation of [3H]ryanodine binding to RYR1, and no change
FT in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 6
FT /note="H->A: Biotinylated MCa: No significant change in
FT stimulation of [3H]ryanodine binding to RYR1, and important
FT increase in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 7
FT /note="L->A: Biotinylated MCa: 2-fold decrease of
FT stimulation of [3H]ryanodine binding to RYR1, and low
FT decrease in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 8
FT /note="K->A: 16-fold decrease of stimulation of
FT [3H]ryanodine binding to RYR1. Biotinylated MCa: 3-fold
FT decrease of stimulation of [3H]ryanodine binding to RYR1,
FT and no change in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT MUTAGEN 9
FT /note="L->A: Biotinylated MCa: 2-fold increase of
FT stimulation of [3H]ryanodine binding to RYR1, and no change
FT in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 12
FT /note="E->A: Biotinylated MCa: 4.8-fold increase of
FT stimulation of [3H]ryanodine binding to RYR1, and very
FT important increase in cell-penetrating properties
FT (PC(50)=113 nM)."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 13
FT /note="N->A: Biotinylated MCa: 2.6-fold increase of
FT stimulation of [3H]ryanodine binding to RYR1, and low
FT decrease in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 15
FT /note="D->A: Biotinylated MCa: 3.7-fold increase of
FT stimulation of [3H]ryanodine binding to RYR1, and no change
FT in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:17888395"
FT MUTAGEN 19
FT /note="K->A: 6-fold decrease of stimulation of
FT [3H]ryanodine binding to RYR1. Biotinylated MCa: 2-fold
FT decrease of stimulation of [3H]ryanodine binding to RYR1,
FT and important decrease in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT MUTAGEN 20
FT /note="K->A: 5-fold decrease of stimulation of
FT [3H]ryanodine binding to RYR1. Biotinylated MCa: 3-fold
FT decrease of stimulation of [3H]ryanodine binding to RYR1,
FT and important decrease in cell-penetrating properties
FT (PC(50)=1350 nM)."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT MUTAGEN 22
FT /note="K->A: 35-fold decrease of stimulation of
FT [3H]ryanodine binding to RYR1. Biotinylated MCa: 4.6-fold
FT decrease of stimulation of [3H]ryanodine binding to RYR1,
FT and low decrease in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT MUTAGEN 23
FT /note="R->A: 13-fold decrease of stimulation of
FT [3H]ryanodine binding to RYR1, but loss of induction of
FT calcium release from sarcoplasmic vesicles. Biotinylated
FT MCa: 9-fold decrease of stimulation of [3H]ryanodine
FT binding to RYR1."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT MUTAGEN 24
FT /note="R->A: Loss of stimulation of [3H]ryanodine binding
FT to RYR1, loss of induction of calcium release from
FT sarcoplasmic vesicles, and loss of induction of long-
FT lasting subconductance state. Biotinylated MCa: Loss of
FT stimulation of [3H]ryanodine binding to RYR1, and low
FT decrease in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT MUTAGEN 26
FT /note="T->A: 4-fold decrease of stimulation of
FT [3H]ryanodine binding to RYR1. Biotinylated MCa: 3.4-fold
FT decrease of stimulation of [3H]ryanodine binding to RYR1."
FT /evidence="ECO:0000269|PubMed:12869557,
FT ECO:0000269|PubMed:17888395"
FT STRAND 9..12
FT /evidence="ECO:0007829|PDB:1C6W"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:1C6W"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:1C6W"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:1C6W"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:1C6W"
SQ SEQUENCE 33 AA; 3865 MW; A5FE70F945FEC8E6 CRC64;
GDCLPHLKLC KENKDCCSKK CKRRGTNIEK RCR
